PDP 406 CLINICAL TOXICOLOGY

Transcription

1 PDP 406 CLINICAL TOXICOLOGY Pharm.D Fourth Year

2 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) Mr.D.Raju.M.Pharm., Lecturer

3 OPTIONS FOR LOCAL IMPLEMENTATION (1) NPC. KEY THERAPEUTIC TOPICS MEDICINES MANAGEMENT OPTIONS FOR LOCAL IMPLEMENTATION. UPDATED JULY 2011 Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients). If initiating an NSAID is obligatory, use ibuprofen (1200mg per day or less) or naproxen (1000mg per day). Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200mg per day or less) or naproxen (1000mg per day).

4 OPTIONS FOR LOCAL IMPLEMENTATION (2) NPC. KEY THERAPEUTIC TOPICS MEDICINES MANAGEMENT OPTIONS FOR LOCAL IMPLEMENTATION. UPDATED JULY 2011 Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and NICE clinical guideline 59 (osteoarthritis). Co-prescribe a proton pump inhibitor with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain in accordance with NICE clinical guidelines 59, 79, and 88. Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with angiotensin converting enzyme (ACE) inhibitors or angiotensin-2 receptor antagonists (A2RAs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.

5 What are the benefits and risks from NSAIDs? How do I reduce the GI risks? How do I reduce the CV risks? Are there specific safety concerns with etoricoxib? What does KEYthe QUESTIONS prescribing REGARDING data Iook like? NSAIDS* *Note by NSAIDs we mean traditional NSAIDs (e.g. diclofenac, naproxen, ibuprofen); etodolac, meloxicam, or coxibs (e.g. celecoxib, etoricoxib)

6 WHAT ARE THE BENEFITS AND RISKS OF NSAIDS?

7 BENEFITS AND RISKS OF NSAIDS NICE Full Clinical Guideline 59: Osteoarthritis. Feb 2008

8 ESTIMATE OF HOSPITAL-RELATED ADMISSIONS DUE TO NSAID ADVERSE REACTIONS BANDOLIER 2000;79:6 8 Event due to NSAID Estimated number of cases per year per primary care group (PCG) Upper GI bleed 18 Acute renal failure 10 Congestive heart failure 22 Information based on an average PCG of 100,000 patients where 3,800 patients aged over 65 years take NSAIDs

9 WHAT ABOUT PARACETAMOL? NICE Full Clinical Guideline 59: Osteoarthritis. Feb 2008 No strong evidence to suggest NSAIDs have a consistent benefit over paracetamol, although some patients obtain greater symptom relief from NSAIDs Clinicians should consider offering paracetamol for pain relief in addition to core treatment; regular dosing may be required Paracetamol (and/or topical NSAIDs) should be considered ahead of oral NSAIDs, COX-2 inhibitors or opioids

10 WHAT DO PATIENTS PREFER? PINCUS T, ET AL. J RHEUMATOL 2000;27: WOLFE F, ET AL. ARTHRITIS RHEUMATOL 2000;43:

11 NSAIDS: RENAL RISKS MHRA DSU. MAY 2009 Renal risk

12 VARIATION AMONG PCTS: QIPP COMPARATOR 5 (1) NSAIDs: ADQ/STAR PU NSAIDs: ADQ/STAR PU (Quarter to to March 2011) 2011 ADQs per Oral NSAIDs STAR(09)-PU Copyright NHSBSA 2011

13 HOW DO I REDUCE THE GI RISKS OF NSAIDS?

14 Ibuprofen offers the lowest GI risk; Coxibs are associated with reduced GI risk relative to most NSAIDs at equivalent doses MeReC Extra 30. November 2007 When offering treatment with an oral NSAID/coxib inhibitor, the first choice should be either a standard NSAID or a coxib (other than etoricoxib 60mg). In either case, these should be coprescribed with a proton pump inhibitor (PPI), choosing the one with the lowest acquisition cost. NICE. Osteoarthritis Guideline CG59. February 2008 NSAIDS: GI RISKS

15 HOW DO I REDUCE THE CV RISKS OF NSAIDS?

16 COXIBS AND CARDIOVASCULAR RISK MHRA. SAFETY OF SELECTIVE AND NON-SELECTIVE NSAIDS OCTOBER 2006 Coxibs are associated with an increased thrombotic risk. Risk varies according to underlying patient risk factors Population risk is about 3 additional events (mainly MI) per 1000 patients per year compared with placebo. Dose-related adverse effects may manifest early and the risk may persist throughout treatment

17 TRADITIONAL NSAIDS AND CV RISK MHRA. SAFETY OF SELECTIVE AND NON-SELECTIVE NSAIDS. OCTOBER 2006 Diclofenac 150mg daily has a similar excess thrombotic risk to that of etoricoxib and possibly other coxibs Naproxen 1000mg daily may be associated with a lower risk of thrombotic events than coxibs. Although some risk with naproxen cannot be entirely ruled out, epidemiological evidence suggests that naproxen is not associated with an excess risk of MI Ibuprofen may be associated with a small thrombotic risk at high doses (e.g. 2400mg daily), whereas at low doses (e.g. 1200mg daily) evidence does not suggest an increased thrombotic risk in the short term

18 FURTHER STUDIES ON CARDIAC SAFETY OF NSAIDS MHRA. DSU FEBRUARY 2009 Two epidemiological studies ( UK THIN database and Danish National Registries) reviewed Increase in thrombotic CV risk may apply to all NSAIDs users, irrespective of their baseline risk, and not only to chronic users Absolute increase in risk for healthy users is very low Current advice remains: patients should use the lowest effective dose and the shortest duration of treatment necessary to control symptoms Overall evidence continues to indicate that naproxen is associated with a lower thrombotic risk than coxibs. For ibuprofen, no significant increase in risk has been identified for doses of up to 1200 mg daily

19 DURATION OF NSAID TREATMENT POST-MI SCHJERNING OLSEN A-M, ET AL. CIRCULATION 2011;123: ; MEREC RAPID REVIEW NO Danish cohort study (n=83,677) of patients post MI Overall, NSAIDs associated with an increased risk of death/recurrent MI Days 0-7 HR 1.45 ( 95% CI 1.29 to 1.62) >90 days HR 1.55 (95% CI 1.46 to 1.64) Increased risk apparent early in treatment Diclofenac associated with the highest risk of death/mi Naproxen associated with the lowest risk of death/mi

20 ETORICOXIB AND BLOOD PRESSURE MHRA. DSU JULY 2008 EMA review of etoricoxib Patients whose BP is persistently above 140/90 mmhg and inadequately controlled must not receive etoricoxib High BP should be controlled before starting treatment, and should be monitored for 2 weeks after the start of treatment and regularly thereafter

21 RECOMMENDATIONS FOR PRESCRIBING OF NSAIDS MEREC EXTRA 30. NOVEMBER 2007 Base on safety profiles of individual NSAIDs and on individual patient risk factors Use lowest effective dose and for shortest period of time necessary to control symptoms Low-dose ibuprofen ( 1200mg per day) is an appropriate first choice NSAID in view of its low risk of GI and CV side effects. Low-dose ibuprofen or naproxen 1000mg/day would appear more appropriate than other NSAIDs for patients in whom CV risk is a significant consideration in decision making Consider prescribing a PPI with any NSAID to reduce the risk of adverse GI effects, particularly in those who are at high GI risk (includes anybody aged 65 years or older) and long-term NSAID users

22 WHAT IS HAPPENING WITH PRESCRIBING?

23 DICLOFENAC PRESCRIBING IN INDIVIDUAL SHAS Data provided by NHSBSA Prescription Services

24 PRESCRIBING OF DICLOFENAC, NAPROXEN AND IBUPROFEN IN ENGLAND Data provided by NHSBSA Prescription Services

25 VARIATION AMONG PCTS: QIPP COMPARATOR 5 NSAIDs: Ibuprofen & Naproxen %items Quarter to March % 32%

26 ITEMS TRENDS IN ETORICOXIB PRESCRIBING IN PRIMARY CARE IN ENGLAND COST Data provided by NHSBSA Prescription Services Dec 2010 to Feb 2011: etoricoxib accounted for 2.7% of the total NSAID items prescribed, but 12.9% ( 2.7 million) of the total costs

27 KEY MESSAGES All NSAIDS (both coxibs and traditional NSAIDs) are associated with CV, renal and GI side effects Where NSAIDs are required, base prescribing on the safety profiles of individual NSAIDs taking into account individual patient risk factors Generally, prescribe NSAIDS at the lowest effective dose and for the shortest period of time necessary to control symptoms. Review prescribing regularly. The risks of CV side effects with diclofenac and coxibs are similar Low-dose ibuprofen and naproxen are associated with the lowest CV risk Consider co-prescribing a PPI with an NSAID, especially to those at high risk of GI side effects, and when used for long-periods of time These slides should be used in conjunction with the accompanying notes